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6
Radioembolization in segmentectomy,
lobectomy, and future liver remnant
hypertrophy
EDWARD KIM, JOSEPH TITANO, AND SAFET LEKPERIC
6.1 Introduction 113
6.2 Treatment planning and delivery 114
6.3 Radiation lobectomy and future liver
remnant hypertrophy 114
6.3.1 Denition and treatment
rationale 114
6.3.2 Radiation biology and
radiation lobectomy 115
6.3.3 Patient selection 116
6.3.4 Lobectomy dosimetry 116
6.3.5 Radiation lobectomy and
the future liver remnant
hypertrophy outcome data 117
6.4 Radiation segmentectomy 119
6.4.1 Denition and treatment rationale 119
6.4.2 Patient selection 120
6.4.3 Segmentectomy dosimetry 120
6.4.4 Radiation segmentectomy
outcome data 120
6.1 INTRODUCTION
As the role of 90Y transarterial radioembolization
has evolved, specic treatment paradigms have led
to the development of radioembolization applications analogous to surgical liver interventions.
e rst such application is “radiation lobectomy,”
in which radioembolization is performed to treat
an unresectable right lobe liver lesion with the
6.5 Radioembolization toxicities and
complications 122
6.5.1 Radiation segmentectomy
toxicities 123
6.6 Posttreatment patient management 123
6.6.1 Patient care in the immediate
postprocedure setting 123
6.6.2 Follow-up evaluation 124
6.6.3 Imaging response 124
6.7 Clinical case examples 124
6.7.1 Sample radiation lobectomy
and the future liver remnant
hypertrophy case 124
6.7.2 Sample radiation
segmentectomy case 126
6.8 Conclusions 128
References 128
threefold intention of treating the tumor, allowing
a biological test of time to select for less aggressive
lesions and causing le lobe hypertrophy as a means
of enabling right lobe surgical resection. e second
analogous concept is “radiation segmentectomy,”
in which a large dose of radiation is delivered to a
small volume of liver thereby imparting a highly
tumoricidal dose to the perfused target, while sparing adjacent and nontarget liver parenchyma. ese
concepts have broadened the armament physicians
113
114 Radioembolization in segmentectomy, lobectomy, and future liver remnant hypertrophy
have available to treat liver tumors by allowing for
treatment of lesions with complex anatomic locations and by expanding the patient population eligible for interventions. e radiation biology, physics,
nuclear medicine, and interventional radiology
concepts related to these treatment entities are discussed in this chapter.
6.2 TREATMENT PLANNING
AND DELIVERY
As described in Chapter 4, once a patient is selected
for radioembolization therapy, treatment planning
begins with the completion of a technetium-99m
macroaggregated albumin (
purpose of this study, again, is multifaceted. First, it
is undertaken to visualize the vascular supply to the
liver and to the lesion of interest. is allows for the
potential embolization of vessels that have the potential to divert the glass or resin 90Y microspheres away
from the intended target thereby causing adverse
events. In addition, it allows for calculation of the
lung shunt fraction (Uliel et al., 2012).
Safe and eective delivery of radioembolization therapy—whether for lobar or segmental
infusion—requires careful evaluation in the interventional suite as well as the patient. Detailed
discussion of radiation safety will be provided in
Chapter 7. Briey, the interventional suite should be
outtted with radiation detection equipment such
that a thin-window Geiger–Müller counter that is
able to detect radiation levels under 0.1 mR/hour is
available to detect the contamination of personnel,
garbage, and the interventional suit equipment.
In addition, an ionization chamber able to detect
radiation doses of 1 mrem/hour should be available to localize the dose delivery site and measure
activity remaining in the dose vial. A large drape
should be prepared in close proximity to the uoroscopy table so that potential leaks are contained
immediately. An acrylic desiccator is also required
in order to house the dose vile, tubing, and catheter
following radioembolization (Salem and urston,
2006c).
Following standard prepping and draping, arterial access is gained—typically via the common
femoral artery. A 4-French or 5-French catheter system is generally utilized to navigate the aorta and to
cannulate the celiac axis or the superior mesenteric
99m
Tc-MAA) study. e
artery. Radioembolization is then generally performed through a coaxial 0.0325-inch system
within the target vessel. During infusion, care must
be taken to avoid stasis and reux of the 90Y microspheres in order to avoid nontarget embolization,
which could result in gastrointestinal ulceration,
lung parenchymal injury, or pancreatitis among
other complications (Salem and urston, 2006c).
Following radioembolization completion and
catheter removal, postprocedure imaging with
single-photon emission computed tomography
(SPECT)/computed tomography (CT) or positron emission tomography (PET)/CT/magnetic
resonance imaging (MRI) may be obtained to
evaluate for nontarget deposition of 90Y microspheres or to assess the distribution of microspheres within the liver and tumor, respectively.
Recently, 90Y PET/CT has gained increasing
popularity compared with 90Y-bremsstrahlung
SPECT/CT on account of its greater dosimetry accuracy (Braat et al., 2015). While further
study is still required, delivered-dose calculation
on posttreatment imaging may predict tumor
response and thereby allow for early planning
of repeat interventions (Braat et al., 2015). More
detailed discussion of these modalities will be
provided in Chapters 10 and 11.
6.3 RADIATION LOBECTOMY
AND FUTURE LIVER
REMNANT HYPERTROPHY
6.3.1 DEFINITION AND TREATMENT
RATIONALE
Radiation lobectomy, as its name implies, entails
lobar infusion of 90Y microspheres. Future liver
remnant (FLR) hypertrophy specically refers to
right lobar delivery of 90Y microspheres in patients
with right-sided tumors who would be candidates
for resection if the FLR were adequate. Adequate
volumes for the FLR have been cited between 20%
and 40% of total liver volume, with a larger remnant recommended for cirrhotic patients (Kubota
etal., 1997; Zorzi et al., 2007; Shindoh et al., 2013;
Vouche et al., 2013). e intention behind radiation lobectomy is threefold: (1) treat the right-sided
tumor, (2) simultaneously induce le liver lobe
hypertrophy such that an adequate FLR is achieved
6.3 Radiation lobectomy / 6.3.2 Radiation biology and radiation lobectomy 115
allowing the patient to proceed with potentially
curative procedures such as surgical resection, and
(3) allow for a test of time to identify less aggressive
tumors in the hopes of limiting recurrence rates
postresection (Gaba et al., 2009; Inarrairaegui
etal., 2012; Salem et al., 2013).
Portal vein embolization (PVE) is an alternative to radiation lobectomy that is also employed
with the intention of inducing lobar hypertrophy
in order to produce an adequate FLR. While PVE
is perhaps even more eective than radioembolization (Azoulay et al., 2000; Pamecha et al., 2009;
Garlipp et al., 2014) at increasing the FLR volume,
there are several advantages oered by radiation
lobectomy. First, PVE does not directly treat the
liver tumor; while it interrupts portal ow to the
lesion, the arterial supply from which tumors draw
the majority of their nutrition remains intact. is
means that lesions remain unchecked while awaiting the FLR hypertrophy following PVE. Radiation
lobectomy is also a microembolic therapy causing
radiation-induced atrophy of the target lobe allowing for a delayed diversion of portal blood ow
from the right lobe to the le lobe, which may allow
for a greater accommodation of increased blood
ow by the FLR (Jakobs et al., 2008; Gaba et al.,
2009; Vouche et al., 2013). is pattern of hypertrophy allows for a test-of-time through which
tumor response to therapy may be assessed and
those patients with positive tumor biology may
then be selected for further curative interventions
(Vouche et al., 2013). Finally, the microembolic
nature of radiation lobectomy allows for expansion
of the treatment population to patients with portal
vein thrombus (PVT). While resection of tumors
associated with PVT is rare in the United States,
these resections are performed frequently in Asian
hospital centers (Vouche et al., 2013).
e combination of transarterial chemoembolization (TACE) and PVE has been oered to account
for the lack of tumor control oered by PVE alone.
While one might expect that embolization of the
portal and arterial vessels supplying the same
region of liver parenchyma may be associated with
hepatic injury, increased toxicity is only transient
(Aoki et al., 2004). In addition to safety, sequential TACE and PVE have been shown to increase
the rate of the FLR hypertrophy, improve recurrence-free survival, and increase overall survival
in patients with hepatocellular carcinoma (HCC)
(Ogata et al., 2006; Yoo et al., 2011). However, the
FLR hypertrophy achieved by the combination of
TACE and PVE is equivalent to or arguably inferior to that of PVE alone (Teo et al., 2015).
6.3.2 RADIATION BIOLOGY AND
RADIATION LOBECTOMY
Before examining the details of liver parenchymal
change followi ng radiation lobectomy, a general discussion of liver tissue response to insult—and specically radiation-induced insult—is warranted. A
more robust discussion of radiation biology can be
found in Chapters 8 and 9. Following parenchymal
injury, hepatic stellate cells migrate to the aected
region and begin to produce extracellular matrix
leading to brosis (Clement et al., 1986; Jakobs
et al., 2008). As shown in studies primarily focused
on external beam radiation, once the radiation
dose applied to liver tissue exceeds 30–40 Gy additional pathological and morphological changes
consistent with veno-occlusive disease (VOD)
are seen including sinusoidal congestion, hemorrhage, atrophy, and necrosis (Fajardo and Colby,
1980; Jakobs et al., 2008). e implication, then,
is that radioembolization may induce a degree of
portal hypertension (Jakobs et al., 2008; Gaba et
al., 2009). e restorative mechanisms associated
with hepatic parenchymal insult are also initiated
following radioembolization. Hepatocyte proliferation is the end result of multiple inputs directed
by cytokines, growth factors, signaling pathway
cascades, and transcription factor activation (Gaba
etal., 2009).
While local veno-occlusive changes follow
radioembolization, radiation lobectomy does not
necessarily induce portal hypertension globally.
In a study by Jakobs et al. (2008), in which volumetric changes following radioembolization were
explored, a subgroup analysis of those patients
who underwent unilateral treatment of the right
liver lobe showed a signicant increase in le liver
lobe volume, a signicant decrease in right liver
lobe volume, increased le portal vein diameter,
and no change in splenic volume. Splenic volumes
were signicantly increased in patients who underwent bilobar radioembolization (Jakobs et al.,
2008). Together, these ndings suggest that portal
venous ow is diverted into the le-sided portal
system—as evidenced by the increased diameter
of the le portal vein—without the development
of secondary signs of portal hypertension such as
116 Radioembolization in segmentectomy, lobectomy, and future liver remnant hypertrophy
an increase in splenic volume following right lobar
radioembolization.
Recently, Fernandez-Ros et al. (2015) described
in detail the mechanisms of the biological response
to radioembolization specically. ey describe
oxidative stress as the driver behind endothelial cell
injury as well as activation of coagulation and proinammatory pathways. While it remains unclear
if the elevation of proinammatory markers is a
primary eect of radioembolization or follows
secondarily from VOD, the role of coagulation in
VOD (as shown in the pathologically similar VOD
following bone marrow transplantation) has been
better established (Fernandez-Ros et al., 2015).
At a cellular level, the changes that have been
described following portal vein ligation and partial
hepatic resection have shown that hepatocytes proliferate initially followed by nonparenchymal cells
(Michalopoulos and DeFrances, 1997; FernandezRos et al., 2015). In addition to the redistribution
of portal blood ow, mitogens including hepatocyte growth factor (HGF), broblast growth factor type 19 (FGF-19), interleukin 6 (IL-6), and
insulin are also increased following these procedures. Specically following radioembolization,
signicant increases in HGF and FGF-19 are noted
(Fernandez-Ros et al., 2015). Both of these factors
drive transcription factor activation and initiate
hepatocyte regeneration. In addition, IL-6 and
tumor necrosis factor-alpha (TNF-α) also drive
hepatocyte replication by initiating the transition
of these cells from G0 to G1 (Fernandez-Ros et
al., 2015). Sustained increases in TNF-α and IL-6
are observed following treatment and likely contribute to the FLR hypertrophy (Fernandez-Ros
et al., 2015). In contrast to TACE following which
transient increases in IL-6 and HGH have been
documented, these factors were noted to be elevated months aer radioembolization—a timeline
commensurate with that of the FLR hypertrophy
(Yamazaki et al., 1996; Kim et al., 2013; FernandezRos et al., 2015). is contrast with TACE also provides a basis for the suggestion that IL-6 and HGH
sustained elevations are more likely the result of
radiation eects than embolic eects of therapy
(Fernandez-Ros et al., 2015).
Radiation lobectomy, then, harnesses multiple
processes leading to both atrophy and hypertrophy
contributing to the therapeutic aim of increasing the
volume of the FLR. e treated right lobe undergoes
the development of sinusoidal congestion, atrophy,
and necrosis while the tumor itself is also treated.
e veno-occlusive changes that follow radioembolization then lead to a slow redirection of portal vein blood ow to the untreated le liver lobe.
Simultaneously then, signaling pathways are initiated and proliferative mediators are recruited while
portal venous ow is directed toward the FLR (Gaba
et al., 2009; Vouche et al., 2013).
6.3.3 PATIENT SELECTION
Generally, radioembolization is indicated for
patients with unresectable HCC, cholangiocarcinoma, or with metastatic liver lesions. In 1999,
the U.S. Food and Drug Administration (USFDA)
issued a humanitarian device exemption for glass
microspheres as neoadjuvant therapy prior to surgery or transplantation in patients with unresectable
HCC. Similarly, in 2002, the USFDA approved the
use of 90Y resin microspheres for the treatment of
unresectable metastatic liver tumors from primary
colorectal cancer with adjuvant intrahepatic artery
chemotherapy.
Against this background, radiation lobectomy
is a specic application of radioembolization in
patients with hepatic tumor lesions that would be
eligible for denitive therapy with hepatic lobar
resection if the remaining FLR were adequate (Gaba
et al., 2009; Siddiqi and Devlin, 2009; Vouche et al.,
2013). Radiation lobectomy allows for the treatment
of right hepatic lobe tumor burden while inducing
the FLR hypertrophy through the redirection of
portal blood ow and by the production of growth
factors and cytokines. In addition, the time interval
required to allow for future remnant hypertrophy
mandates a period prior to surgical intervention
that allows for aggressive tumors to declare themselves on follow-up imaging (Vouche et al., 2013).
6.3.4 LOBECTOMY DOSIMETRY
Generally, dose calculation for radiation lobectomy and the FLR hypertrophy is performed by
completing calculations for lobar therapy as discussed in Chapter 5. Briey, under assumptions of
uniform dose distribution and complete 90Y decay
as elaborated upon in the previous chapter, the
administered activity is calculated using Equation
5.9 where Ao is the treatment activity, D
desired average absorbed dose, and M
mass of the liver to be treated:
is the
avg
is the
liver
6.3 Radiation lobectomy / 6.3.5 Radiation lobectomy and FLR hypertrophy outcome data 117
(Gy) (kg)
49.98(Js)
gl
DM
⋅
⋅
GBq1 1 49.98(Js)
(kg)
liver
ASFR
M
()
()()
−−⋅⋅
LLPV
TLPV
=⋅
%FLR Hypertrophy
(GBq)
A
o
av
=
iver
Again, the lobar mass is utilized as the mass of
liver intended to undergo treatment in this dose
calculation paradigm. e mass of the liver to be
treated, M
, is obtained by measuring the target
liver
liver volume and converting the volume measure
to a calculated mass value 1.05 kg/L.
Following treatment, the actual dose delivered
may be determined utilizing Equation 6.1:
D
delivered
Gy
()
o
=
(6.1)
where SF is the lung shunt fraction and R is the
percentage of dose remaining within the vial at the
completion of treatment. Currently, there is no universal dosing pattern for radiation lobectomy and
the FLR hypertrophy. e dosing information in the
major studies of radiation lobectomy is provided in
Table 6.1. In the largest study of resin microspheres
utilized for radiation lobectomy and the FLR hypertrophy, Fernandez-Ros et al. (2014) found no correlation between dose and volume changes and
concluded that—while it is currently unknown
increased dosing could enhance the FLR hypertrophy—hypertrophy does indeed occur at therapeutic
doses. Similarly, in the largest study of glass microspheres used for radiation lobectomy and the FLR
hypertrophy, Vouche et al. (2013) reported a median
dose of 112 Gy (range: 74–215 Gy) delivered to the
treatment site and included dose ≤100 Gy and dose
>120 Gy as variables in their multivariate analysis of
%FLR hypertrophy (dened below), with neither of
the conditions meeting statistical signicance.
resonance imaging (SHARP or VIBE sequences) or
computed tomography. Boundaries for the right lobe
and the le lobe were delineated by the le hepatic
vein in the upper lobe and a line drawn from the
inferior vena cava to the insertion of the falciform
ligament in the lower lobes. e portal triad, gallbladder, and inferior vena cava were excluded from
volumetric analysis. According to this system, the
right liver lobe volume consists of the combined
measures of segments 1, 4, 5, 6, 7, and 8 while the le
liver lobe volume consists of the combined measures
of segments 2 and 3.
While usage of the term FLR has been dened
in several ways, we have selected to dene it as the
percentage of the FLR volume as a ratio of total
liver volume (Vouche et al., 2013). Integral to the
discussion of liver volume changes following radiation lobectomy are the following equations:
FLR%
FLRFLR
post-Y90pre-Y90
=
FLR
pre-Y90
100%
⋅–100%,
(6.2)
(6.3)
where LLPV is dened as the volume of segments 2
and 3 less the total volume of tumor within the le
lobe, and TLPV is dened as the total liver volume
less the volume of total tumor burden within the
liver (Vouche et al., 2013).
6.3.5.2 Liver volume changes,
subsequent therapies, and
survival outcomes
6.3.5 RADIATION LOBECTOMY
6.3.5.1 Imaging response
In the assessment of the FLR hypertrophy, volumetric measures of liver parenchyma are obviously
essential. In the largest cohort of glass microsphere
radiation lobectomy cases, Vouche et al. (2013) completed computer-assisted volumetric assessment of
the liver on either gadolinium-enhanced magnetic
AND THE FUTURE LIVER
REMNANT HYPERTROPHY
OUTCOME DATA
Several studies have evaluated the ecacy of radiation lobectomy in producing the FLR hypertrophy. e ndings of these studies are provided in
Table 6.1. Jakobs et al. (2008) evaluated volumetric
changes in the liver following lobar treatment with
90
Y in a cohort predominantly of colorectal metastasis cases; a subanalysis of the those patients who
received unilateral right lobar treatment revealed
signicantly decreased right lobe volume with subsequent le lobe hypertrophy and no signicant
increase in spleen volume (Jakobs et al., 2008).
ese ndings contributed to the notion that
radiation lobectomy allowed for a gradual, wellcompensated diversion of portal venous ow from
118 Radioembolization in segmentectomy, lobectomy, and future liver remnant hypertrophy
Future
resection or
transplantation
Overall
survival
summary
Imaging response
volume
Time to
measure FLR hypertrophy
unilobar CRC
metastases
went on to
right
hepatectomy
NR One patient with
right lobe CR 2, PR 14,
PD 1; bilobar disease
group left lobe PR 1,
SD 4, PD 12; unilobar
group right lobe PR 4,
RECIST, r disease group
34%
Mean 47%, median
median 36
days
Mean 44 days,
SD 2, PD 1
NR
months
Median 13.5
29.6%, PD 7.4%
mRECIST
CR 29.6%, PR 33.3%, SD
months
3 months Mean 29% at 3
NR NR NR
available time
points
Mean 42% at all
approximately
NR NR
RECIST
CR 1, PR 19, SD 5, PD 1
45%
(standard
deviation
22.9%), median
Mean 29%
days (27–79
days)
Median 46
underwent
surgical right
NR One patient
PD 4
RECIST, CR 2, PR 5, SD 6,
25.3%
(standard
deviation 34.9%;
Mean 34.2%
months
(range 2–12
lobectomy
range
19.0–106.5%)
months),
mean 5.7
months
Five patients
NR NR NR
1–12 months Mean 50.46% at 6
NR Median
months, mean
56.49% at 12
months
1–9+ months Median maximal
underwent
surgical right
lobectomy; 6
patients
survival
BCLC B
and C
patients
FLR 26%,
median 45% at
> 9 months
(5–186)
underwent
OLT
was 34.4
and 9.6
months,
respectively
Number
Table 6.1 Radiation lobectomy and the FLR hypertrophy selected studies
information
GBq, median
Activity/dose
Single or multiple
Micro-
Patient age
of
activity 1.75
Mean activity 1.67
treatments
treatments 4–6
weeks apart for
spheres
Resin Staged lobar
breast 5,
pancreatic
CRC 15,
(years) Tumor path
(range
44–78)
24 Median 63
patients
dehfar et al.
(2013)
Ahmadza-
Study
GBq (range
0.40–3.90
Gbq), dose NR
17 patients with
bilobar disease;
single treatment
for 7 patients
with unilobar
2, gastric
1, unknown
primary 1
treated
disease
Single Median dose to
Resin 4
34 NR HCC Glass 30,
(2013)
Edeline et al.
segment 122.1
Gy (90.4–210.5
Gy)
Resin Single NR 4–26+ weeks Mean
HCC 52, CRC
83 Median 66
Fernandez-Ros
Resin Single Median activity 1.2
13, IHC 4,
Other 14
CRC 18,
(IQR
53–79)
26 Mean 59.2
et al. (2014)
Garlipp et al.
GBq (range
0.8–1.7 GBq)
Dose NR
Breast 8,
Other 6
(standard
deviation
11.1)
(2014)
HCC Resin Single NR Median 5
(42–78)
17 Median 72
(2014)
Teo et al.
right lobe 112
Gy (range
100–160 Gy)
HCC Glass Single Mean dose to
(range
55–90)
45 Mean 71.9
(2014)
Theysohn etal.
treatment site
112 Gy (range
74–215 Gy)
Glass Single Median dose to
8, CRC 8
HCC 67, IHC
(range
36–89)
83 Median 68
(2013)
Vouche et al.
Note: CR, complete response; CRC, col orectal can cer; IQR, interquartile r ange; NR, not repo rted; PD, progres sive disease; PR , partial resp onse; SD, stable d isease.
6.4 Radiation segmentectomy / 6.4.1 Denition and treatment rationale 119
the right lobe to the FLR without inducing global
portal hypertension.
A study by Gaba et al. (2009) provided similar
results in a cohort of HCC and cholangiocarcinoma cases with statistically signicant increases
and decreases in le lobe and right lobe volumes,
respectively, measured at an average of 18 months
posttreatment (Gaba et al., 2009). Similarly,
Vouche et al. (2013) demonstrated statistically signicant lobar volume changes and showed a linear,
time-dependent hypertrophy of the FLR. In their
cohort of 83 patients, 5 went on to lobar resection
and 6 underwent liver transplantation. Vouche et
al. (2013) also showed that volumetric changes are
apparent as early as 1 month posttreatment with
maximum FLR hypertrophy achieved at approximately 9 months posttreatment. Interestingly, the
presence of portal vein thrombosis was a signicant predictor of the FLR hypertrophy >40% with
the implication that existing portal vein thrombus might act as a naturally occurring portal vein
embolization with even earlier diversion of portal
ow to the FLR (Vouche et al., 2013).
In addition to portal vein thrombus predicting increased FLR hypertrophy, a recent study by
Teo et al. (2014) showed that HCC patients with
underlying hepatitis B may achieve greater FLR
hypertrophy than their counterparts with hepatitis C or alcoholic liver disease. is nding, combined with a trend observed by Fernandez-Ros et
al. (2014) toward reduced the FLR hypertrophy,
implies that cirrhosis may somewhat limit the benets of lobectomy in generating FLR hypertrophy.
Survival data for studies focused on radiation
lobectomy and FLR hypertrophy specically are
reported at up to a median of 36.6 months and
are in line with concurrently published prospective and retrospective cohorts (Gaba et al., 2009;
Vouche et al., 2013).
6.4 RADIATION
SEGMENTECTOMY
6.4.1 DEFINITION AND TREATMENT
RATIONALE
Radiation segmentectomy is dened as radioembolization of two or fewer hepatic segments—as
delineated by the Couinaud system—during a
single treatment session (Rhee et al., 2005; Riaz
etal., 2011). e term segmentectomy was utilized
in reference to the resultant atrophy of the treated
segments seen at follow-up imaging, which is analogous to segmental surgical hepatic resection.
Several factors created the clinical need for
radiation segmentectomy. First, small tumors
(those ≤3 cm) are generally considered for cura-
tive therapies including transplantation, surgical
resection, and ablation (Llovet et al., 1999). If, however, a lesion is not amenable to curative intervention on account of anatomic considerations (e.g.,
adjacent to the dome of the liver and diaphragm
or in close proximity to large vessels), comorbidities, or inadequate functional liver reserve, radiation segmentectomy remains a viable treatment
option for these patients. Second, several authors
have shown that increased radiation dose is associated with improved tumor response (Ben-Josef
etal., 2005; Riaz et al., 2011; Vouche et al., 2014),
and radiation segmentectomy allows for greater
activity delivery directly to a target lesion. Further,
it has also been theorized that lower radiation dose
applied to normal hepatic parenchyma minimizes
injury to the normal tissue allowing for greater
physiologic regeneration of normal parenchyma
(Riaz et al., 2011).
In direct comparison with ablative procedures,
there are several advantages and disadvantages to
radiation segmentectomy. Advantages of radiation segmentectomy include the obviation of percutaneous needle and probe placement with the
associated theoretical risk of tract seeding and the
ability to target high-risk ablation lesions (Riaz
et al., 2011; Vouche et al., 2014). Disadvantages
of segmentectomy relative to ablative procedures
potentially include cost and radiation exposure,
although ablation probes are oen placed with
CT guidance making this a relative disadvantage
(Vouche et al., 2014).
In addition to its complimentary role with other
ablative therapies, radiation segmentectomy also
has several advantages compared with externalbeam radiation therapy. ese advantages are
mainly linked to anatomic and practical considerations regarding treatment planning and delivery.
Lesions within the caudate lobe and the dome of
the liver put adjacent structures such as the lung
parenchyma and porta hepatis ducts and vessels
at increased risk (Riaz et al., 2011). In addition,
while dose fractionation has shown benets in
120 Radioembolization in segmentectomy, lobectomy, and future liver remnant hypertrophy
targeting radiosensitive as well as resistant malignant cells, this therapeutic approach requires multiple treatment sessions (Riaz et al., 2011). A nal
practical consideration is that respiratory motion
potentially puts lung parenchyma at risk during
external-beam radiation delivery in a manner that
is avoided with transarterial delivery of radiation
with the maximum tissue penetration of 11 mm
associated with 90Y (Salem and urston, 2006a;
Riaz et al., 2011).
6.4.2 PATIENT SELECTION
Based on the denition of radiation segmentectomy, a lesion must be isolatable within only two
segments of the liver supplied by the hepatic arterial vessel selected for delivery of 90Y microspheres.
As discussed above, segmentectomy is complimentary to ablation in that suboptimal lesions for ablation may be treated by radiation segmentectomy.
e most oen cited reason that a lesion is deferred
for ablation is that a lesion is located at the dome of
the liver in close proximity to the diaphragm and
lung tissue (Riaz et al., 2011). Additional anatomic
considerations leading to the choice of radiation
segmentectomy over ablation include proximity
to vessels and biliary structures, caudate lobe location, and proximity to small bowel, large bowel,
the gallbladder, or the heart (Vouche et al., 2014).
Recent publications have also demonstrated the
safety and ecacy of radiation segmentectomy in
patients with moderate hepatic dysfunction and
advanced disease including portal vein invasion
(Padia et al., 2014).
to a tumor is complicated by the physiology of
blood ow to liver tumors and to normal hepatic
parenchyma. First, the formulae applied for dose
calculations oen assume uniform distribution
of microspheres within the treated volume of
liver. However, it has been shown through a number of modalities that blood ow is preferentially
diverted toward tumor compared with normal
liver parenchyma (Lau et al., 1994; Ho et al., 1996;
Campbell et al., 2000; Sarfaraz et al., 2003; Riaz
etal., 2011). Intuitively, this matches an essential
tenant of transarterial liver tumor therapy that
liver tumors draw a majority of their blood supply from the hepatic arterial system while normal
parenchyma receives a majority of its blood supply
from the portal venous system.
Attempts to account for the nonuniform distribution of blood ow—and therefore of 90Y microspheres—have been made previously. Riaz et al.
(2011) identied the problems associated with the
assumption of uniformity in microsphere distribution and sought to account for these issues by
incorporating a subjectively determined ratio of
tumor hypervascularity relative to adjacent normal
liver tissue following a review of angiography and
cross-sectional imaging studies. Although not an
ideal means of quantifying the asymmetric distribution of blood ow to tumor relative to surrounding normal tissue, this method demonstrated that
such dierences in calculation lead to more than
doubling of the median calculated dose delivered
to tumor—from 521 Gy (95% CI: 404–645 Gy) to
1214 Gy (95% CI: 961–1546 Gy) in their cohort of
84 patients (Riaz et al., 2011).
6.4.3 SEGMENTECTOMY
DOSIMETRY
Generally, dose calculation for radiation segmentectomy is performed by completing calculations
intended for treatment of the entire lobe in which
the lesion is located; however, intra-arterial injection of the lobar dose is performed from a segmental vessel supplying one or two segments as
described previously (Rhee et al., 2005; Vouche et
al., 2014). Equation 5.9 may be utilized in order to
calculate the activity to be delivered.
Following treatment, the actual dose delivered may be determined utilizing Equation 6.1.
However, accurate calculation of activity delivered
6.4.4 RADIATION
SEGMENTECTOMY
OUTCOME DATA
6.4.4.1 Radiation segmentectomy
imaging response
Imaging response in the studies focused on the
methodology of radiation segmentectomy is summarized in Table 6.2. Riaz et al. (2011) presented
imaging response in accordance with World
Health Organization (WHO) and European
Association for the Study of the Liver (EASL)
guidelines. EASL response was reported in 81%
follow-up of 275
90% at median
summary Overall survival
Imaging response
days (range 5–133 days).
Time to EASL response: 33
6.4 Radiation segmentectomy / 6.4.4 Radiation segmentectomy outcome data 121
days (range
32–677 days)
EASL: CR 19, SD 1
NR NR
survival 26.9
months (95% CI,
20.5–30.2
months)
Median overall
9.3–18.7 months); EASL:
response in 81% of
patients; median time to
response 1.2 months
(95% CI, 1.1–1.4 months);
WHO: response in 59% of
survival
uncensored 53.4
months; median
overall survival
Median overall
patients; median time to
response 7.2 months
(95% CI, 4.2–8.5 months)
SD 12%, PD 1%
mRECIST: CR 47%, PR 39%,
censored for
transplantation
34.5 months
Micro-
spheres Dose Follow-up time
path
Tumor
(years)
Patient age
of
patients
Number
days (range
32 –677 days)
Median 275
segment 254 Gy
(range 105–1055 Gy),
median dose to
tumor 536 Gy (range
HCC Glass Median dose to
(range
54–76)
20 Median 61
days (range
35–600 days)
Median 185
203–1618 Gy)
segment 348 Gy
(range 105–857 Gy)
HCC Glass Median dose to
(range
41–78)
14 Mean 62
NR TTP 13.6 months (95% CI,
segment 521 Gy
(range 404–645 Gy)
HCC Glass Median dose to
(43–90)
84 Median 68
months
Median 27.1
segment 242 Gy
(IQR, 173–369 Gy)
HCC Glass Median dose to
(IQR,
58–74)
102 Median 64
Table 6.2 Radiation segmentectomy selected studies
Study
(2014)
Padia et al.
(2005)
Rhee et al.
Riaz et al.
(2011)
Vouche etal.
(2014)
Note: CR , complete resp onse; IQR, inter quartile range; NR, not repo rted; PD, progres sive disease; PR , partial response; SD, stable disease; T TP, t ime to progression; WHO, World Health Organi zation.
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